Inhibition of diethylnitrosamine-induced rat liver chromosomal aberrations and DNA-strand breaks by synergistic supplementation of vanadium and 1α,25-dihydroxyvitamin D3

AbstractVanadium (V) has recently been found to possess potent anti-neoplastic activity in rat hepatocarcinogenesis. Recent studies have suggested that the active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], can inhibit growth and/or induce differentiation of a variety of cell types. In the present study, attempts have been made to investigate the combination effects on chromosomal aberrations (CAs) and DNA-strand breaks during the early preneoplastic stage of diethylnitrosamine (DEN)-induced rat liver carcinogenesis in male Sprague-Dawley rats. V (0.5 ppm ad libitum) and/or 1,25(OH)2D3 (0.3 μg/0.1 ml propylene glycol per os twice weekly) either alone or in combination were given to DEN-treated and control rats 4 weeks prior to DEN injection. Under these experimental conditions it was observed that, when given in combination, V and 1,25(OH)2D3 offered maximum protection against DEN-induced structural aberrations 96 h (66.7%, P<0.05), 15 days (44.9%, P<0.005) and 30 days (63.8%, P<0.001) after DEN injection. Synergistic supplementation of both V and 1,25(OH)2D3 4 weeks before DEN injection was found to offer significant (64.1%, P